Trident technique of safe nuclear emulsification in posterior polar cataracts.

The common complications associated with a posterior polar cataract (PPC) with deficient or weak posterior capsules (PCs) are posterior capsular rupture (PCR), vitreous loss, and luxation of lens material into the vitreous. Often the commonly used technique of hydrodelineation in such cataracts can lead to accidental hydrodissection, and even the slightest nucleus rotation during phacoemulsification can cause the PC to give way. We describe a modified relatively safe technique (Trident technique) for managing the nucleus in PPCs which does not involve any hydroprocedure or nucleus rotation.

Understanding the implications of under-reporting, vaccine efficiency and social behavior on the post-pandemic spread using physics informed neural networks: A case study of China.

In late 2019, the emergence of COVID-19 in Wuhan, China, led to the implementation of stringent measures forming the zero-COVID policy aimed at eliminating transmission. Zero-COVID policy basically aimed at completely eliminating the transmission of COVID-19. However, the relaxation of this policy in late 2022 reportedly resulted in a rapid surge of COVID-19 cases. The aim of this work is to investigate the factors contributing to this outbreak using a new SEIR-type epidemic model with time-dependent level of immunity. Our model incorporates a time-dependent level of immunity considering vaccine doses administered and time-post-vaccination dependent vaccine efficacy. We find that vaccine efficacy plays a significant role in determining the outbreak size and maximum number of daily infected. Additionally, our model considers under-reporting in daily cases and deaths, revealing their combined effects on the outbreak magnitude. We also introduce a novel Physics Informed Neural Networks (PINNs) approach which is extremely useful in estimating critical parameters and helps in evaluating the predictive capability of our model.

A mathematical modeling technique to understand the role of decoy receptors in ligand-receptor interaction.

The ligand-receptor interaction is fundamental to many cellular processes in eukaryotic cells such as cell migration, proliferation, adhesion, signaling and so on. Cell migration is a central process in the development of organisms. Receptor induced chemo-tactic sensitivity plays an important role in cell migration. However, recently some receptors identified as decoy receptors, obstruct some mechanisms of certain regular receptors. DcR3 is one such important decoy receptor, generally found in glioma cell, RCC cell and many various malignant cells which obstruct some mechanism including apoptosis cell-signaling, cell inflammation, cell migration. The goal of our work is to mathematically formulate ligand-receptor interaction induced cell migration in the presence of decoy receptors. We develop here a novel mathematical model, consisting of four coupled partial differential equations which predict the movement of glioma cells due to the reaction-kinetic mechanism between regular receptors CD95, its ligand CD95L and decoy receptors DcR3 as obtained in experimental results. The aim is to measure the number of cells in the chamber's filter for different concentrations of ligand in presence of decoy receptors and compute the distance travelled by the cells inside filter due to cell migration. Using experimental results, we validate our model which suggests that the concentration of ligands plays an important role in cell migration.

Important signs to check posterior capsule integrity.

For beginner surgeons, it is difficult to recognize the posterior capsule during cataract surgery. In the case of brown cataracts with a thin posterior capsule and in cataracts with asteroid hyalosis, it is difficult to identify the capsule before intraocular lens (IOL) implantation even for expert surgeons. Here we illustrate five important signs, which can be practiced in routine cases to make sure the posterior capsule is intact, before IOL implantation.

Visual outcomes and complications of manual small-incision cataract surgery in patients with pseudoexfoliation.

Purpose: Pseudoexfoliation is an age-related fibrillopathy characterized by the deposition of fibrillar material in the eye with an increased risk of complications during cataract surgery. Aim was to study visual outcomes and complications in patients with pseudoexfoliation undergoing manual small-incision cataract surgery (MSICS). Methods: Prospective observational study was performed on 152 patients with pseudoexfoliation above 50 years undergoing MSICS in a tertiary hospital from December 2016 to November 2017. Intraoperative and postoperative complications were documented with follow-up on postoperative day 1, 1st week, 1st month, and 3rd month. Results: Preoperative small pupil was noted in 49 eyes (32.2%), and 19 (12.5%) required intraoperative measures. Intraocular complications noted were zonular dialysis in five (3.3%), posterior capsular rupture in one (0.7%), and iridodialysis in one (0.7%). On postoperative day 1, the most common complication was corneal edema in 134 patients but clinically significant in only 23 (15.1%). Postoperative complications at 3 months were irregular pupil in 17 cases and decentered IOL in three cases. Intraocular pressure decreased with each visit [preoperative mean: 14.39 (±3.4) and 13.37 (±2.0) 12.53 (±1.4) mm Hg at 1 and 3 months, respectively]. There was a significant improvement in vision from the first day mean pinhole vision of 0.26 (±0.24) to mean best corrected visual acuity (BCVA) of 0.09 (±0.22) and 0.07 (±0.22) at 1 and 3 months, respectively. Mean endothelial cell loss was 193.16 (7.79%) and 266.01 (10.68%) at 1 and 3 months, respectively. Conclusion: Pseudoexfoliation has an increased risk of complications during cataract surgery. MSICS gives good outcomes in terms of visual recovery and postoperative outcomes.

Promoting the Importance of Recall Visits Among Dental Patients in India Using a Semi-Autonomous AI System.

In many developing countries like India, there is a widespread lack of general awareness about the importance of good oral health, which causes dental patients to neglect their oral hygiene, thus precipitating many long-term ailments. We developed an application that promotes the significance of regular dental checkups and oral health care by explaining to patients how these are intrinsic to overall health. Our application, in essence, extracts relevant health information from published scientific studies according to a patient's medical history and shares it with the patient at the discretion of the supervising dentist, thereby empowering patients to make more informed decisions. We present a detailed overview of our semi- autonomous machine learning-based solution, along with the complex challenges involved in the design, development, and real-world deployment of our application. Finally, we conducted a randomized parallel-group study in India with 224 dental patients over two years to assess the utility of our proposed solution. Results show our application improved the patient recall rate from 21.1% to 37.8% (p-value = 0.024).

The Hard Lessons and Shifting Modeling Trends of COVID-19 Dynamics: Multiresolution Modeling Approach.

The COVID-19 pandemic has placed epidemiologists, modelers, and policy makers at the forefront of the global discussion of how to control the spread of coronavirus. The main challenges confronting modelling approaches include real-time projections of changes in the numbers of cases, hospitalizations, and fatalities, the consequences of public health policy, the understanding of how best to implement varied non-pharmaceutical interventions and potential vaccination strategies, now that vaccines are available for distribution. Here, we: (i) review carefully selected literature on COVID-19 modeling to identify challenges associated with developing appropriate models along with collecting the fine-tuned data, (ii) use the identified challenges to suggest prospective modeling frameworks through which adaptive interventions such as vaccine strategies and the uses of diagnostic tests can be evaluated, and (iii) provide a novel Multiresolution Modeling Framework which constructs a multi-objective optimization problem by considering relevant stakeholders' participatory perspective to carry out epidemic nowcasting and future prediction. Consolidating our understanding of model approaches to COVID-19 will assist policy makers in designing interventions that are not only maximally effective but also economically beneficial.

Analytical Estimation of Data-Motivated Time-Dependent Disease Transmission Rate: An Application to Ebola and Selected Public Health Problems.

Obtaining reasonable estimates for transmission rates from observed data is a challenge when using mathematical models to study the dynamics of ?infectious? diseases, like Ebola. Most models assume the transmission rate of a contagion either does not vary over time or change in a fixed pre-determined adhoc ways. However, these rates do vary during an outbreak due to multitude of factors such as environmental conditions, social behaviors, and public-health interventions deployed to control the disease, which are in-part guided by changing size of an outbreak. We derive analytical estimates of time-dependent transmission rate for an epidemic in terms of either incidence or prevalence using a standard mathematical SIR-type epidemic model. We illustrate applicability of our method by applying data on various public health problems, including infectious diseases (Ebola, SARS, and Leishmaniasis) and social issues (obesity and alcohol drinking) to compute transmission rates over time. We show that time-dependent transmission rate estimates can have a large variation, depending on the type of available data and other epidemiological parameters. Time-dependent estimation of transmission rates captures the dynamics of the problem better and can be utilized to understand disease progression more accurately.

Dynamics of prion proliferation under combined treatment of pharmacological chaperones and interferons.

Prions are proteins that cause fatal neurodegenerative diseases. The misfolded conformation adopted by prions can be transmitted to other normally folded proteins. Therapeutics to stop prion proliferation have been studied experimentally; however, it is not clear how the combination of different types of treatments can decrease the growth rate of prions in the brain. In this article, we combine the implementation of pharmacological chaperones and interferons to develop a novel model using a non-linear system of ordinary differential equations and study the quantitative effects of these two treatments on the growth rate of prions. This study aims to identify how the two treatments affect prion proliferation, both individually and in tandem. We analyze the model, and qualitative global results on the disease-free and disease equilibria are proved analytically. Numerical simulations, using parameter values from in vivo experiments that provide a pharmaceutically important demonstration of the effects of these two treatments, are presented here. This mathematical model can be used to identify and optimize the best combination of the treatments within their safe ranges.

Perfect anterior capsulorhexis using a dented cystitome.

We describe a novel intraoperative technique of measuring and creating an adequate size continuous curvilinear capsulorhexis (CCC) in phacoemulsification, using a dented cystitome as the ruler. A pair of curved tenotomy scissors is used to create a dent on the cystitome at a distance of 2.5 mm length (i.e., half of the desired approximate capsulorhexis diameter). The dented cystitome is used as a guide for making a CCC of approximately 5 mm diameter, which is considered adequate for phacoemulsification. This method of measuring the capsulorhexis helps in achieving a well centered and stable intraocular lens with a 360° overlap of the optic edge by the anterior capsular rim in the postoperative period. Using a dented cystitome for capsulorhexis mandates reliable and consistent results in the hands of the novice as well as the experienced surgeons.

The role of oxygen intake and liver enzyme on the dynamics of damaged hepatocytes: Implications to ischaemic liver injury via a mathematical model.

Ischaemic Hepatitis (IH) or Hypoxic Hepatitis (HH) also known as centrilobular liver cell necrosis is an acute liver injury characterized by a rapid increase in serum aminotransferase. The liver injury typically results from different underlying medical conditions such as cardiac failure, respiratory failure and septic shock in which the liver becomes damaged due to deprivation of either blood or oxygen. IH is a potentially lethal condition that is often preventable if diagnosed timely. The role of mechanisms that cause IH is often not well understood, making it difficult to diagnose or accurately quantify the patterns of related biomarkers. In most patients, currently, the only way to determine a case of IH is to rule out all other possible conditions for liver injuries. A better understanding of the liver's response to IH is necessary to aid in its diagnosis, measurement, and improve outcomes. The goal of this study is to identify mechanisms that can alter associated biomarkers for reducing the density of damaged hepatocytes, and thus reduce the chances of IH. We develop a mathematical model capturing dynamics of hepatocytes in the liver through the rise and fall of associated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) related to the condition of IH. The model analysis provides a novel approach to predict the level of biomarkers given variations in the systemic oxygen in the body. Using IH patient data in the US, novel model parameters are described and then estimated for the first time to capture real-time dynamics of hepatocytes in the presence and absence of IH condition. The results may allow physicians to estimate the extent of liver damage in an IH patient based on their enzyme levels and receive faster treatment on a real-time basis.

The role of alcohol consumption on acetaminophen induced liver injury: Implications from a mathematical model.

Acetaminophen (APAP) overdose is one of the predominant causes of drug induced acute liver injury in the U.S and U.K. Clinical studies show that ingestion of alcohol may increase the risk of APAP induced liver injury. Chronic alcoholism may potentiate APAP hepatotoxicity and this increased risk of APAP toxicity is observed when APAP is ingested even shortly after alcohol is cleared from the body. However, clinical reports also suggest that acute alcohol consumption may have a protective effect against hepatotoxicity by inhibiting microsomal acetaminophen oxidation and thereby reducing N-acetyl-p-benzoquinone imine (NAPQI) production. The aim of this study is to model this dual role of alcohol to determine how the timing of alcohol ingestion affects APAP metabolism and resulting liver injury and identify mechanisms of APAP induced liver injury. The mathematical model is developed to capture condition of a patient of single time APAP overdose who may be an acute or chronic alcohol user. The analysis suggests that the risk of APAP-induced hepatotoxicity is increased if APAP is ingested shortly after alcohol is cleared from the body in chronic alcohol users. A protective effect of acute consumption of alcohol is also observed in patients with APAP overdose. For example, simultaneous ingestion of alcohol and APAP overdose or alcohol intake after or before few hours of APAP overdose may result in less APAP-induced hepatotoxicity when compared to a single time APAP overdose. The rate of hepatocyte damage in APAP overdose patients depends on trade-off between induction and inhibition of CYP enzyme.

Understanding reproductive health challenges during a flood: insights from Belkuchi Upazila, Bangladesh.

Background: Bangladesh is exposed to natural hazards such as floods, cyclones and droughts. As such, its health systems and health infrastructure are exposed to recurrent disasters. Research studying the impacts of natural disasters on reproductive health in particular is lacking. This research contributes to this knowledge gap by studying the challenges related to menstrual regulation and post-abortion care at both the facility and community levels, and the care-seeking patterns of pregnant women during the 2016 flood in Belkuchi, Bangladesh. Methods: Six government-run primary health care facilities were assessed using a structured assessment tool prior to the flood of 2016. In total, 370 structured interviews were conducted with women in three unions of Belkuchi (Belkuchi Sadar, Daulatpur and Bhangabari) 4 months after the 2016 flood. Results: The main challenges at the facility level are a lack of services and a shortage of medicines, equipment and trained health workers. The main challenges at the community level are displacement, high rates of self-diagnosed spontaneous abortion and a lack of treatment for post-abortion complications. A majority of the interviewed women (48%) sought menstrual regulation from the residence of a nurse or family welfare visitor. In total, 73.2% of the women who experienced post-abortion complications sought medical care. Conclusion: To overcome the challenges at the facility level, it is important to construct flood-resistant health infrastructure and train health workers in menstrual regulation and post-abortion care, so that these services can be made available during a flood. At the community level, more research is required to understand the reasons for spontaneous abortions so that these, and the subsequent chronic conditions/complications women experience, may be avoided. Context specific interventions that can overcome local challenges (both at the community and facility levels) are required to promote disaster resilience at primary health care facilities.

Pediatric leukemia: Moving toward more accurate models.

Leukemia is a complex genetic disease caused by errors in differentiation, growth, and apoptosis of hematopoietic cells in either lymphoid or myeloid lineages. Large-scale genomic characterization of thousands of leukemia patients has produced a tremendous amount of data that have enabled a better understanding of the differences between adult and pediatric patients. For instance, although phenotypically similar, pediatric and adult myeloid leukemia patients differ in their mutational profiles, typically involving either chromosomal translocations or recurrent single-base-pair mutations, respectively. To elucidate the molecular mechanisms underlying the biology of this cancer, continual efforts have been made to develop more contextually and biologically relevant experimental models. Leukemic cell lines, for example, provide an inexpensive and tractable model but often fail to recapitulate critical aspects of tumor biology. Likewise, murine leukemia models of leukemia have been highly informative but also do not entirely reproduce the human disease. More recent advances in the development of patient-derived xenografts (PDXs) or human models of leukemias are poised to provide a more comprehensive, and biologically relevant, approach to directly assess the impact of the in vivo environment on human samples. In this review, the advantages and limitations of the various current models used to functionally define the genetic requirements of leukemogenesis are discussed.

The impact of time from diagnosis to treatment in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires treatment. We retrospectively analyzed the impact of time from diagnosis-to-treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in 581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01) and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern Cooperative Oncology Group ≥2 (p = .02), stage 3-4 disease (p < .001), and longer TDT (HR 1.12, p = .028) predicted shorter PFS. The significant interactions between TDT with lactate dehydrogenase (LDH) and with disease stage prompted separate analyses in high versus normal LDH, and stage 3-4 versus 1-2 disease. Longer TDT was associated with shortened PFS and OS only with advanced stage, and, if high LDH was present. Treatment should be started as early as possible for high-tumor burden disease. Delaying treatment in patients with early stage or low LDH does not seem harmful.

Continuous-wave and quasi-continuous wave thulium-doped all-fiber laser: implementation on kidney stone fragmentations.

A continuous-wave (CW) as well as quasi-continuous wave (QCW) thulium-doped all-fiber laser at 1.94 µm has been designed for targeting applications in urology. The thulium-doped active fiber with an octagonal-shaped inner cladding is pumped at 793 nm to achieve stable CW laser power of 10 W with 32% lasing efficiency (against launched pump power). The linear variation of laser power with pump offers a scope of further power scaling. A QCW operation with variation of duty cycle from 0.5% to 90%, repetition rate from 0.1 Hz to 1 kHz, and pulse width from 40 µs to 2 s has been presented. Laser power of 9.5 W in CW mode of operation and average power of 5.2 W with energy range of 10.4-104 mJ in QCW mode of operation has been employed to fragment calcium oxalate monohydrate kidney stones (size of 1.5-4 cm) having different colors and composition. Dependence of ablation threshold, ablation rate, and average fragmented particle size on the average power and energy has been studied. One minute of laser exposure results in fragmentation of a stone surface with ablation rate of 8 mg/min having minimum particle size of 6.54 µm with an average size of 20-100 µm ensuring the natural removal of fragmented parts through the urethra.

Characterization of the autophosphorylation property of HflX, a ribosome-binding GTPase from Escherichia coli.

Escherichia coli HflX belongs to the widely distributed but poorly characterized HflX family of translation factor-related GTPases that is conserved from bacteria to humans. A 426-residue polypeptide that binds 50S ribosomes and has both GTPase and ATPase activities, HflX also exhibits autophosphorylation activity. We show that HflX(C), a C-terminal fragment of HflX, has an enhanced autophosphorylation activity compared to the full-length protein. Using a chemical stability assay and thin layer chromatography, we have determined that phosphorylation occurs at a serine residue. Each of the nine serine residues of HflX(C) was mutated to alanine. It was found that all but S211A retained autophosphorylation activity, suggesting that S211, located in the P-loop, was the likely site for autophosphorylation. While the S211A mutant lacked the autophosphorylation site, it possessed strong GTP binding and GTPase activities.

Novel MntR-independent mechanism of manganese homeostasis in Escherichia coli by the ribosome-associated protein HflX.

Manganese is a micronutrient required for activities of several important enzymes under conditions of oxidative stress and iron starvation. In Escherichia coli, the manganese homeostasis network primarily constitutes a manganese importer (MntH) and an exporter (MntP), which are regulated by the MntR dual regulator. In this study, we find that deletion of E. coli hflX, which encodes a ribosome-associated GTPase with unknown function, renders extreme manganese sensitivity characterized by arrested cell growth, filamentation, lower rate of replication, and DNA damage. We demonstrate that perturbation by manganese induces unprecedented influx of manganese in ΔhflX cells compared to that in the wild-type E. coli strain. Interestingly, our study indicates that the imbalance in manganese homeostasis in the ΔhflX strain is independent of the MntR regulon. Moreover, the influx of manganese leads to a simultaneous influx of zinc and inhibition of iron import in ΔhflX cells. In order to review a possible link of HflX with the λ phage life cycle, we performed a lysis-lysogeny assay to show that the Mn-perturbed ΔhflX strain reduces the frequency of lysogenization of the phage. This observation raises the possibility that the induced zinc influx in the manganese-perturbed ΔhflX strain stimulates the activity of the zinc-metalloprotease HflB, the key determinant of the lysis-lysogeny switch. Finally, we propose that manganese-mediated autophosphorylation of HflX plays a central role in manganese, zinc, and iron homeostasis in E. coli cells.